Long-Term Outcomes with Islet-Alone and Islet-after-Kidney Transplantation for Type 1 Diabetes in the Clinical Islet Transplantation Consortium: the CIT08 Study
To determine long-term outcomes for islet-alone and islet-after-kidney transplantation in adults with type 1 diabetes complicated by impaired awareness of hypoglycemia.
RESEARCH DESIGN AND METHODS
Prospective interventional and observational cohort study of islet-alone (n =48) and islet-after-kidney (n =24) transplant recipients followed for up to 8-years after intraportal infusion of one or more Purified Human Pancreatic Islet products under standardized immunosuppression. Outcomes included duration of islet graft survival (stimulated C-peptide ≥0.3 ng/mL), on-target glycemic control (HbA1c <7.0%), freedom from severe hypoglycemia, and insulin-independence.
Of the 48 islet-alone and 24 islet-after-kidney recipients, 26 and 8 completed long-term follow-up with islet graft function, 15 and 7 withdrew from follow-up with islet graft function, and 7 and 9 experienced islet graft failure, respectively. Actuarial islet graft survival at median and final follow-up was 84 and 56% for islet-alone and 69 and 49% for islet-after-kidney (P =0.007) with 77 and 49% of islet-alone and 57 and 35% of islet-after-kidney recipients maintaining post-transplant HbA1c <7.0% (P =0.0017); freedom from severe hypoglycemia was maintained at >90% in both cohorts. Insulin-independence was achieved by 74% of islet-alone and islet-after-kidney recipients with more than half maintaining insulin-independence during long-term follow-up. Kidney function remained stable during long-term follow-up in both cohorts and rates of sensitization against human leukocyte antigens were low. Severe adverse events occurred at 0.31 per patient-year for islet-alone and 0.43 per patient-year for islet-after-kidney.
Islet transplantation results in durable islet graft survival permitting achievement of glycemic targets in the absence of severe hypoglycemia for most appropriately indicated recipients having impaired awareness of hypoglycemia with acceptable safety of added immunosuppression for both islet-alone and islet-after-kidney transplantation.